Molecular docking and charge density analysis were carried out to understand the geometry, charge density distribution and electrostatic properties of one of newly synthesized 4-substituted-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates (PDE), which is regarded as the best [Formula: see text]-Glucosidase inhibitor among the hydropyridine dicarboxylate derivatives. The different bonding models of the PDE molecule in the active sites of proteins Human serum albumin (HSA) and Saccharomyces cerevisiae [Formula: see text]-glucosidase (SAG) are firstly compared, which is important to understand the different intermolecular interactions between drug-transport protein and drug-target protein. The deformation density maps suggest that the electron densities of the PDE molecule are redistributed when it presents in the active sites. When the molecule presents in the active site of the SAG, it is evident to find that the negative region does not appear at the vicinity of the oxygen atoms on one of the carboxylic acid dimethyl ester group. Frontier molecular orbital density distributions for the PDE molecule are similar in all forms. The highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) energy gaps in the active sites are higher than that of the molecule in pure solution phase. It is generally noticed that all of the orientations of the dipole moment vectors are reoriented in both active sites. These fine details at electronic level allow to better understand the exact drug-transport protein and drug-target protein interactions.
